MAP2K2
小结
MAP2K2（也称为MEK2）编码蛋白是一种丝氨酸/苏氨酸激酶，在促分裂原活化蛋白激酶（MAPK）信号级联中起着效应蛋白的作用。MAPK信号通路参与多种细胞过程的调控，包括增殖、分化、细胞粘附和转录。作为三层MAPK级联的一个组成部分，MAP2K2活性依赖于上游RAF激酶的磷酸化。活化的MAP2K2依次对作为转录调节子ERK1/2（胞外信号调节激酶1/2）磷酸化。这些信号传导由激活上游受体酪氨酸激酶的生长因子、细胞因子和激素触发，最终导致细胞生长、分化、增殖和存活的关键调节因子的表达改变。MAPK通路的过度激活在人类癌症中经常被观察到，然而，原发肿瘤中MAP2K2的致癌突变比较罕见。
MAP2K2 (also known as MEK2) is a serine/threonine kinase that functions as an effector protein in the mitogen-activated protein kinase (MAPK) signaling cascade. The MAPK signaling pathway is involved in the regulation of diverse cellular processes including proliferation, differentiation, cell adhesion and transcription. As a component of a three-tiered MAPK cascade, MEK2 activity is dependent on phosphorylation by upstream RAF kinases. Activated MEK2 in turn phosphorylates ERK1/2 (extracellular-signal-regulated kinases1/2) which then serves as a transcriptional regulator. These signaling events are triggered by growth factors, cytokines, and hormones that activate upstream receptor tyrosine kinases, ultimately leading to altered expression of key regulators of cell growth, differentiation, proliferation and survival. Germline missense mutations and deletions in MEK2 are found in patients with cardio-facio-cutaneous syndrome. Hyperactivation of the MAPK pathway is frequently observed in human cancers; however, oncogenic mutations in MAP2K2 in primary tumors are infrequent. Because of its major role in signaling as a RAF oncogene effector, several inhibitors of wildtype MEK2 and its close structural and functional homolog, MEK1, have been developed. The MEK1/2 inhibitors trametinib and cobimetinib are FDA-approved for the treatment of melanoma in combination with RAF inhibition and preclinical and clinical efforts are ongoing to determine the efficacy of MEK1/2 inhibition for other indications. Mutations in MEK2 have been identified in melanomas insensitive to RAF and MEK inhibition and may mediate resistance to MAPK pathway targeted agents.